Recent evidence from animal and human studies indicates that cortical structures play an important role in the perception of pain. In addition, it has been shown that following nociceptive deafferentation, the forebrain undergoes somatotopic reorganization which can modify the cortical processing of pain perception, and lead to chronic pain and hyperalgesia. In this subproject, we propose to investigate the cortical generators of pain perception in normal subjects and to identify the reorganizational changes in the central nociceptive system that occur following deafferentation and following the development of chronic pain. This will be accomplished by recording the cerebral potentials following cutaneous stimulation with noxious pulses from a CO2 laser. This method is especially suited for the stated aim because laser pulses selectively activate peripheral nociceptive afferents (A-delta and C nociceptors) and the amplitude of the recorded cerebral potentials correlates parametrically with the magnitude of pain perception in humans. The subjects will consist of a group of normal volunteers, another composed of patients with spinal cord injuries and a third consisting of patients with brachial plexus injuries. The testing of normal volunteers will allow us to identify and measure the components of laser evoked pain- related cerebral potentials that best correlate with the magnitude of pain perception and to define the localization of their cerebral dipoles and temporal sequence of their activation. Longitudinal testing of both groups of patients prior to and following the development of chronic pain will help distinguish the changes in pain-related cerebral potentials that follow nociceptive deafferentation from those seen in the setting of chronic pain. The testing of patients with chronic pain following pharmacological intervention will be evaluated by correlating effectiveness of drug treatment with specific alteration in the laser evoked pain-related cerebral potentials. These results could have therapeutic as well as prognostic implications for patients with nociceptive deafferentation and chronic pain. The proposed research will enhance our understanding of the forebrain mechanisms of pain perception and help define the reorganizational changes that occur following deafferentation and the development of chronic pain which might have therapeutic as well as prognostic implications. It will also establish the usefulness of laser evoked pain-related cerebral potential recordings in assessing the integrity of the nociceptive system and in evaluating the efficacy of pharmacological intervention for the treatment of pain.